Is UMPS p.Leu339= (c.1017A>G) pathogenic?

UMPS p.Leu339= (c.1017A>G) is classified Likely benign in UMPS (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-09). Ultra-rare (popmax 0.0828%, afr); Associated with Hereditary orotic aciduria, type 1.

What condition is associated with UMPS p.Leu339= (c.1017A>G)?

UMPS p.Leu339= (c.1017A>G) is associated with Hereditary orotic aciduria, type 1 (ClinVar).

How common is UMPS p.Leu339= (c.1017A>G) in the general population?

UMPS p.Leu339= (c.1017A>G) is ultra-rare (popmax 0.0828%, afr) (gnomAD).

UMPS p.Leu339=

c.1017A>G · rs371015972 · VCV728436

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0828%, afr)

Conditions

Hereditary orotic aciduria, type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.9	GERP -5.5
Overall
CADD	0.929	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0828% African / African-American · 62/74,906 alleles

Filtering AF 0.0662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0603%

Overall 0.00508% 82/1,614,044 alleles · ultra-rare exomes 49/1,461,882 · genomes 33/152,162 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0828%	1,208
Middle Eastern	0.0165%	6,076
East Asian	0.0156%	6,413
Admixed American	0.0133%	7,500
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	8.47e-05%	1,180,050

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: UMPS
Protein: p.Leu339=
Coding: c.1017A>G
MANE Select: NM_000373
dbSNP: rs371015972
Type: single nucleotide variant
Location: chr3:124740058 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.36 · 125 PDB
Residue 339: the 'ompdecase' region; a β-strand

Full UMPS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Hereditary orotic aciduria, type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UMPS p.Ala4Pro Uncertain significance ★★ ⚠ same condition
UMPS p.Arg313Trp Uncertain significance ★★ ⚠ same condition
UMPS p.Gly167Arg Uncertain significance ★★ ⚠ same condition
UMPS p.Ser276Asn Uncertain significance ★★ ⚠ same condition
UMPS p.Ser404Phe Uncertain significance ★★ ⚠ same condition
UMPS c.1159-19C>T Likely benign ★★ same condition
UMPS c.*28A>G Benign ★★ same condition
UMPS p.Gly213Ala Benign ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/umps-p-leu339 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown